Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Role for UL12.5 and nucleic acid sensing in Phase I HSV reactivation

Award Number: R21AI171544
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2023
PERIOD OF PERFORMANCE END DATE: 10/31/2026

Group Awards By:

View Award Description

Role for UL12.5 and nucleic acid sensing in Phase I HSV reactivation - Herpes simplex virus (HSV) establishes a lifelong latent infection of neurons, periodically reactivating to produce infectious virus. Reactivation can cause keratitis and lesions on the body surface. Furthermore, substantial data link HSV to the progression of Alzheimer's disease, highlighting the need to develop therapeutics to prevent HSV reactivation. However, little is known about the mechanisms regulating the induction of viral gene expression following a reactivation stimulus. Previous studies from our lab and others have shown that HSV reactivation is biphasic, with an initial synchronous burst of viral gene expression, referred to as Phase I or animation because it is unique to the reactivation process. Viral gene expression during Phase I/animation is independent of viral DNA replication and requires the host cell stress protein, DLK. When initially discovered, Phase I/animation was also thought not to require HSV lytic proteins. However, our lab has found that at least one viral protein, UL12.5, is required to promote expression of additional viral genes during Phase I, suggesting that the process of animation is more complex than previously thought. However, unlike the events during HSV lytic replication, the timing of viral gene expression and promoters used during Phase I/animation have not been elucidated. Therefore, the goals of this project are to map HSV lytic gene expression during animation and determine the contributions of DLK and UL12.5 to ultimately promoting Phase I gene expression. The only known function of UL12.5 is to induce mitochondrial nucleic acid release and subsequent activation of innate immune sensing pathways involving STING and/or MAVS. Intriguingly, we have found that direct activation of STING can induce HSV to reactivate from a latent infection. Therefore, based on our preliminary data, we hypothesize that UL12.5 is expressed early during animation to hijack innate sensing pathways and promote Phase I viral lytic gene expression. In aim 1), we will map at high resolution the lytic transcriptional units expressed during animation and the contribution of the only known host (DLK) and viral (UL12.5) factors important for Phase I gene expression. In aim 2), we will test the hypothesis that HSV hijacks innate sensing pathways for Phase I gene expression. This proposal is significant and innovative because we will create the first high-resolution map of HSV lytic gene expression following a reactivation stimulus, facilitating future investigation into the role of viral genes and host proteins in promoting exit from latency. In addition, we will determine the contribution of the first viral protein identified that is required for HSV Phase I gene expression. Inhibiting UL12.5 expression or its downstream mechanism of action could prevent entry into reactivation and, therefore, limit potential detrimental effects of UL12.5 or additional viral proteins that could ultimately promote neuronal degeneration.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $192,065 )
2025	2025	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	001	2	8/28/2025	NON-COMPETING CONTINUATION	$0
2025	2025	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	2	11/18/2024	NON-COMPETING CONTINUATION	$192,065
														Subtotal = $192,065

Issue Date FY: 2024 ( Subtotal = $238,380 )
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	1	11/27/2023	NEW	$214,542
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	001	1	9/11/2024	NEW	$23,838
														Subtotal = $238,380

Grand Total All Awards = $430,445

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Role for UL12.5 and nucleic acid sensing in Phase I HSV reactivation

Award Number: R21AI171544

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/01/2023

PERIOD OF PERFORMANCE END DATE: 10/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer